This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS), together, lead to the death of more than four million people annually, world-wide. AIDS is a substantial contributor to TB reactivation. Robust animal models of TB, AIDS and TB-AIDS co-infection will be crucial for the development of vaccines and treatments for these diseases. It has been possible to model AIDS extremely well in rhesus macaques infected with simian immunodeficiency virus (SIV). These macaques undergo a rapid decline in the CD4+ T cell levels in peripheral blood and various lymphoid tissues following infection, and develop chronic to acute AIDS characterized by severe immune deficiency. Infection of macaques with Mtb produces a variety of outcomes, including primary fulminate TB, chronic, slowly progressive TB, or latent infection, thus accurately recapitulating the host-driven diversity of human TB. We have recently demonstrated the capability to infect rhesus macaques with a high- or low-dose of aerosolized Mtb, producing active pulmonary TB and latent disease, respectively. The ability to infect macaques with Mtb via the aerosol route will allow us to model TB as closely as possible to natural disease. In this study, we will combine our recently developed aerosol-based model of TB in rhesus macaques, with the existing SIV infection model in the same species, in order to study the clinical, immunological, molecular and pathological parameters of co-infection between SIV and Mtb.